Cardiometabolic disease including cardiovascular disease and diabetes mellitus, is a leading cause of death that has killed approximately 38 million people worldwide. Although monocytes and macrophages play central roles in atherosclerosis and related CMD, we have yet to realize monocyte targeted therapeutics from human CMD. In collaboration with Dr. Muredach Reilly at Columbia University, we are performing single-cell RNA-seq profiling of human monocytes coupled to innovative population genetics and functional genomics to define the role of human monocyte subpopulations inhuman monocyte-macrophage biology and CMD. We hope to address a major knowledge gap in human monocyte biology by defining the landscape of human monocyte subpopulations, their regulatory features, genetic association with CMD, and functional genomics in human model systems.